Considering gene therapy to protect from X‐linked deafness DFNX2 and associated neurodevelopmental disorders

peer reviewedMutations and deletions in the gene or upstream of the gene encoding the POU3F4 transcription factor cause X‐linked progressive deafness DFNX2 and additional neurodevelopmental disorders in humans. Hearing loss can be purely sensorineural or mixed, that is, with both conductive and sensorineural components. Affected males show anatomical abnormalities of the inner ear, which are jointly defined as incomplete partition type III. Current approaches to improve hearing and speech skills of DFNX2 patients do not seem to be fully effective. Owing to inner ear malformations, cochlear implantation is surgically difficult and may predispose towards severe complications. Even in cases where implantation is safely performed, hearing and speech outcomes remain highly variable among patients. Mouse models for DFNX2 deafness revealed that sensorineural loss could arise from a dysfunction of spiral ligament fibrocytes in the lateral wall of the cochlea, which leads to reduced endocochlear potential. Highly positive endocochlear potential is critical for sensory hair cell mechanotransduction and hearing. In this context, here, we propose to develop a therapeutic approach in male Pou3f4−/y mice based on an adeno‐associated viral (AAV) vector‐mediated gene transfer in cochlear spiral ligament fibrocytes. Among a broad range of AAV vectors, AAV7 was found to show a strong tropism for the spiral ligament. Thus, we suggest that an AAV7‐ mediated delivery of Pou3f4 complementary DNA in the spiral ligament of Pou3f4−/y mice could represent an attractive strategy to prevent fibrocyte degeneration and to restore normal cochlear functions and properties, including a positive endocochlear potential, before hearing loss progresses to profound deafness

Dire l’entreprise, c’est la modéliser dans sa complexité

L’entreprise ne peut se dire et être dite que par les modèles que l’on en construit : si elle a un projet, elle n’est pas un objet passif et sans nécessité. L’enjeu central est lié aux représentations que l’on se fait de l’entreprise. Les théories de l’organisation ont fourni quelques modèles de références dans la logique desquels se sont développées de nombreuses actlvités qui dominent encore intensément nos cultures entrepreneuriales et donc aussi la communication de l’entreprise, l’article propose de substituer un autre mode de pensée permettant de passer du modèle à la modéllsation. Quelques propriétés fondamentales des systèmes organisés et organisants sont pointées pour déboucher sur la bouclé conceptuelle organisation-information, articulée autour du processus de mémorisation.À firm can only express itself and be expressed through the models that are made of it. If it has a project then it is not a passive, unnecessary object. The central concern is linked to the representations which are made of a flrm. Organization theories have supplled a few reference models from which have developed numerous activities which still intensely dominate our business culture and also business communication strategies. The article proposes to substitute another way of thinking which would pass from the model to modelllng. À few fundamental characteristics of organised and organising systems are identified in order to arrivé at the organisation-information conceptual loop which turns on the process of mémorisation

Cochlear connexin 30 homomeric and heteromeric channels exhibit distinct assembly mechanisms.

Many of the mutations in GJB2 and GJB6, which encode connexins 26 and 30 (Cx26 and Cx30), impair the formation of membrane channels and cause autosomal syndromic and non-syndromic hearing loss. In cochlear non-sensory supporting cells, Cx26 and Cx30 form two types of homomeric and heteromeric gap junctions. The biogenesis processes of these channels occurring in situ remain largely unknown. Here we show that Cx30 homomeric and Cx26/Cx30 heteromeric gap junctions exhibit distinct assembly mechanisms in the cochlea. When expressed as homomeric channels, Cx30 preferentially interacts with beta-actin in the peripheral non-junctional membrane region, called perinexus, and strongly relies on the actin network for gap junction plaque assembly. In contrast, we found that Cx26/Cx30 heteromeric gap junction plaques are devoid of perinexus and associated actin network, and resist to actin-depolymerizating drug. This supports that Cx26/Cx30 oligomers could be directly delivered from the interior of the cell to the junctional plaque. Altogether, our data provide a novel insight in homomeric and heteromeric gap junction plaque assembly in the cochlea

Perspectives économiques 2008 - 2009

Depuis près d’un an maintenant, l’économie belge est secouée par des vents contraires. Malgré cela, elle a fait preuve jusqu’à présent d’une assez bonne résilience eu égard aux chocs encaissés. Ceci fut encore confirmé au premier trimestre de 2008. Gare cependant aux excès d’optimisme ! Les évolutions récentes de l’environnement économique mondial et des indicateurs prospectifs de l’économie belge attestent davantage qu’il y a trois mois la perspective d’un ralentissement de l’économie en 2008 et en première partie de 2009.

Mineralogical and hydrogeological study of "pouhons" in the lower Palaeozoic formations of the Stavelot-Venn Massif, Belgium

peer reviewedNumer ous natur ally CO 2-rich mineral water springs, locally called pouhons, occur in the Stavelot-Venn Massif. These water springs show a particular composition with a high content of iron, manganese and lithium, and are characterised by a redorange colour resulting from iron hydroxide precipitation near the land surface. Radon measurements have shown that these ferruginous deposits are weakly radioactive. The Upper Cambrian black shales of the La Gleize Formation are also known to display radioactive anomalies. These rocks show enrichment in HFSE (Pb, U, Y, Ce, Zr, Ti, Nb) and are depleted in transition metals (Co, Ni, Cu, Zn). Specific minerals such as florencite-(Ce), monazite-(Ce), xenotime-(Y) and zircon have been identified and are probably at the origin of the radioactive anomalies. Uranium was gradually leached from these minerals, transported in solution, and finally concentrated in ferruginous muds. These muds are mainly composed of goethite (most often amorphous), residual quartz and calcite in some samples. The most probable hypothesis is that uranium is adsorbed in small concentrations on the goethite surface. On the other hand, the Ottré Formation (Ordovician) appears to be the main source of lithium, iron and manganese. Pouhon waters have therefore probably leached rocks of various mineralogy and chemical composition during their sub-surface circulation

A Large-Scale Distribution of Milk-Based Fortified Spreads: Evidence for a New Approach in Regions with High Burden of Acute Malnutrition

BACKGROUND: There are 146 million underweight children in the developing world, which contribute to up to half of the world's child deaths. In high burden regions for malnutrition, the treatment of individual children is limited by available resources. Here, we evaluate a large-scale distribution of a nutritional supplement on the prevention of wasting. METHODS AND FINDINGS: A new ready-to-use food (RUF) was developed as a diet supplement for children under three. The intervention consisted of six monthly distributions of RUF during the 2007 hunger gap in a district of Maradi region, Niger, for approximately 60,000 children (length: 60-85 cm). At each distribution, all children over 65 cm had their Mid-Upper Arm Circumference (MUAC) recorded. Admission trends for severe wasting (WFH<70% NCHS) in Maradi, 2002-2005 show an increase every year during the hunger gap. In contrast, in 2007, throughout the period of the distribution, the incidence of severe acute malnutrition (MUAC<110 mm) remained at extremely low levels. Comparison of year-over-year admissions to the therapeutic feeding program shows that the 2007 blanket distribution had essentially the same flattening effect on the seasonal rise in admissions as the 2006 individualized treatment of almost 60,000 children moderately wasted. CONCLUSIONS: These results demonstrate the potential for distribution of fortified spreads to reduce the incidence of severe wasting in large population of children 6-36 months of age. Although further information is needed on the cost-effectiveness of such distributions, these results highlight the importance of re-evaluating current nutritional strategies and international recommendations for high burden areas of childhood malnutrition

AquaCrop and the Belgian collaborative agriculture monitoring (BELCAM) platform

peer reviewe

Crop Phenology Modelling Using Proximal and Satellite Sensor Data

peer reviewedUnderstanding crop phenology is crucial for predicting crop yields and identifying potential risks to food security. The objective was to investigate the effectiveness of satellite sensor data, compared to field observations and proximal sensing, in detecting crop phenological stages. Time series data from 122 winter wheat, 99 silage maize, and 77 late potato fields were analyzed during 2015–2017. The spectral signals derived from Digital Hemispherical Photographs (DHP), Disaster Monitoring Constellation (DMC), and Sentinel-2 (S2) were crop-specific and sensor-independent. Models fitted to sensor-derived fAPAR (fraction of absorbed photosynthetically active radiation) demonstrated a higher goodness of fit as compared to fCover (fraction of vegetation cover), with the best model fits obtained for maize, followed by wheat and potato. S2-derived fAPAR showed decreasing variability as the growing season progressed. The use of a double sigmoid model fit allowed defining inflection points corresponding to stem elongation (upward sigmoid) and senescence (downward sigmoid), while the upward endpoint corresponded to canopy closure and the maximum values to flowering and fruit development. Furthermore, increasing the frequency of sensor revisits is beneficial for detecting short-duration crop phenological stages. The results have implications for data assimilation to improve crop yield forecasting and agri-environmental modeling

Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes

A deficiency in pejvakin, a protein of unknown function, causes a strikingly heterogeneous form of human deafness. Pejvakin-deficient (Pjvk(-/-)) mice also exhibit variable auditory phenotypes. Correlation between their hearing thresholds and the number of pups per cage suggest a possible harmful effect of pup vocalizations. Direct sound or electrical stimulation show that the cochlear sensory hair cells and auditory pathway neurons of Pjvk(-/-) mice and patients are exceptionally vulnerable to sound. Subcellular analysis revealed that pejvakin is associated with peroxisomes and required for their oxidative-stress-induced proliferation. Pjvk(-/-) cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in Pjvk(-/-) hair cells show structural abnormalities after the onset of hearing. Noise exposure rapidly upregulates Pjvk cochlear transcription in wild-type mice and triggers peroxisome proliferation in hair cells and primary auditory neurons. Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage